Zinc Finger 259 Gene Polymorphism rs964184 is Associated with Serum Triglyceride Levels and Metabolic Syndrome

Metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors that include: abdominal obesity, dyslipidaemia, hypertension, insulin resistance and impaired glucose tolerance. Recent genome wide association studies have identified several susceptibility regions involved in lipid metabolism that are also associated with MetS. We have explored the association of 9 genetic polymorphisms involved in lipid metabolism and hypertension, including: MTHFR C677T, SELE L554F, FGB - 455G>A, GNB3 C825T, ZNF259 C>G, PSRC-1 A>G, CETP I405V, LPL S447X and LPA C>T in 97 subjects with MetS and 96 individuals without MetS who were recruited randomly from Mashhad stroke and heart atherosclerotic disorder (MASHAD) study using a stratified cluster random sampling technique. Anthropometric parameters and biochemical measurements were determined in all the subjects. Genotyping was carried out followed by univariate and multivariate analyses. The subjects with MetS had a higher triglyceride and lower HDL- C. CG+ GG genotypes of ZNF259 polymorphism (rs964184 C>G) and TT+CT genotypes of MTHFR C677T (rs1801133) were associated with MetS, and individuals carrying the G allele for ZNF259 or the T allele for MTHFR polymorphisms were associated with MetS (e.g, odds ratio (OR) for CG+GG genotypes vs. CC wild type: 2.52, CI=1.33-4.77; P=0.005). However, after multiple comparison adjustment, this relationship remained significant only for CG+ GG genotypes of ZNF259 polymorphism. Moreover, the ZNF259 CG+ GG genotypes were associated with increased serum concentrations of triglycerides and LDL-C, compared to the wild type. These data support the necessity for further studies in larger multicenter settings.

impaired glucose tolerance. It is associated with an increased risk of cardiovascular disease (CVD) and diabetes mellitus (1). Over the past decades, the number of people with MetS has increased globally.
The prevalence of MetS in the Iranian adult population (95% confidence interval) is approximately 32.1% (31.2-33. which are known to play a key role in lipid metabolism (4)(5)(6)(7)(8). Lipoprotein (a) consists of a cholesterol-laden low-density lipoprotein (LDL)like particle bound to a plasminogen-like glycoprotein, apolipoprotein (a). Lipoprotein (a) has been shown to be associated with thrombosis and atherosclerosis, and genetic data support a role for lipoprotein (a) in atherosclerotic stenosis and MetS (9)(10)(11).
Lipoprotein lipase (LPL) plays an important role in lipid metabolism and is expressed in the myocardium, adipose tissue and skeletal muscle (12). It catalyzes the hydrolysis of triacylglycerol present in chylomicron particles and VLDL (13).
This reaction provides free fatty acids and monoacylglycerol for use by skeletal, cardiac muscle and adipose tissue. The LPL gene is located on the short (p) arm of chromosome 8 at position 22. A common variant S447X (rs328) was reported at carrier frequencies of approximately 10 to 25% or higher frequencies in some populations (14)(15).
CETP has been reported to have an association with CVD and its exact role in disease pathogenesis is unclear. CETP plays a key role in cholesteryl ester transfer from HDL-C to TG-rich lipoproteins. CETP polymorphisms are also associated with MetS (16) and increased level of TG and lower HDL-C levels (3). The CETP gene is located on the long (q) arm of chromosome 16 at position 21. It has been shown previously that polymorphisms in the CETP gene are related to increased risk for CAD (17)(18).
High plasma concentration of homocysteine may predispose individuals to atherosclerosis by injuring the vascular endothelium, which might result in hypertension (19)(20)(21). The MTHFR gene is located on the short (p) arm of chromosome 1 at position 36.3. Another candidate gene, which might be involved with hypertension, is fibrinogen.
Fibrinogen is a soluble glycoprotein, which is synthesized in the hepatocyte. Plasma fibrinogen is a dimer composed of three polypeptide chains, α, β and γ that are coded by three genes FGA, FGB and FGG, respectively (22,23). It has been shown that plasma fibrinogen levels are associated with CVD, however, the role of genetic variation in the etiology of MetS still remains conflicting (22,23).
The FGB gene is located on the long (q) arm of chromosome 4 at position 28. The rs1800790 (-455 G/A) polymorphism within the promoter of FGB gene has been shown to be related with increasing plasma fibrinogen concentration (22,24). Several studies have been reported that the L554F allele (rs5355) is associated with a higher risk of developing atherosclerosis and increased blood pressure risk in overweight individuals (27)(28). In 1998, a common single nucleotide polymorphism (SNP), rs5443 (C825T) (thymidine to cytosine change), located on exon 10 of the GNB3 gene was identified to be associated with CVD (29,30).
Several studies have shown that the T allele of the

Phenotypic definition of metabolic syndrome
We used the IDF criteria to define MetS.

Anthropometric and Biochemical Measurements
Anthropometric parameters (height, body weight, waist and hip circumference) were measured as described previously (36,37). Body mass index (BMI) was calculated as body weight

Characteristics of the population
The baseline characteristics of the individuals with and without MetS are summarized in Table 1.